Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus.

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease with uncertain pathogenesis. Endoplasmic reticulum (ER) stress has close correlations with inflammation and/or immune diseases. However, it is unknown whether aberrant ER stress is involved in SLE pathogenesis. We aimed to characterize the ER stress-related genes in patients with SLE and analyzed their correlations with the disease. Peripheral blood leucocytes were isolated from 76 well-characterized patients with SLE and 69 healthy controls. ER stress-related genes were determined at transcription level by absolute quantitative real-time polymerase chain reaction. Stepwise regression and correlation analysis were used to analyze the relationships between SLE disease and ER stress. Abnormal unfolded protein responses were found in patients with SLE with the downregulation of inositol-requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK) and CCAAT/enhancer-binding protein homologous protein (CHoP) and upregulation of XBP1, XBP1s and MANF. In the patients with SLE disease activity index (SLE-DAI)